The Regulatory Sciences Department is offering this grant to optimize clinical approaches for topical drug bioequivalence.

The primary objective of this funding opportunity is to optimize clinical study designs and data analysis techniques that can support a comparative assessment of the relative bioavailability of topically administered drugs, and which can support a demonstration of BE for prospective generic topical products. The specific aims of this research would include comparing in vivo cutaneous PK measurements by independent techniques (e.g., dermal Open Flow Microperfusion (dOFM), dermal microdialysis (dMD), spectroscopic tomography), exploring the removal of the topical formulations at different time points and characterizing the PK profiles of the test and reference products; developing data analysis techniques (described in detail below); and identifying appropriate PK endpoints for the evaluation of topical BE. Based on the multidisciplinary nature of the research supported by this funding opportunity, it is encouraged that researchers with expertise in measuring cutaneous drug concentrations (e.g., experts in techniques such as dOFM, dMD and/or spectroscopy based techniques) collaborate with experts in PK data analysis and with statisticians, to achieve the overall objectives of the research. Specific areas of scientific interest would include the following:

1. Expansion of the current theoretical framework to describe the relationship between the concentration of drug sampled by a given technique (dOFM, dMD, or spectroscopy based techniques) and the actual amount of drug in the epidermis/dermis, and the relationships between the free drug vs protein-bound drug sampled, when relevant, so that not only could the relative amounts of drug in the epidermis/dermis be compared, but also that the actual drug exposures at the site of action could be calculated.

2. Comparison of the available techniques for characterizing cutaneous PK in parallel, within the same clinical setting. (e.g., comparison of dOFM or dMD with other technique(s) that monitor cutaneous PK, like spectroscopic tomography, ideally using commercially available instrumentation).

3. Exploration of different study designs to characterize the cutaneous PK profiles for topical drugs that may not reach the maximum drug concentration (Cmax) within the 24 hours of administration.

4. Development and implementation of data analysis strategy(ies), including statistical assessments of cutaneous PK data for the methods explored within the scope of this research, including identifying appropriate PK endpoints for establishing BE using cutaneous PK based approaches.